tbuckley/cabot-search huggingface dataset:
Survival patterns based on site-specific visceral metastasis in patients with metastatic prostate cancer: Are outcomes of visceral metastases the same?
Authors: Mohamed E. Ahmed, Jack R. Andrews, Ahmed Mahmoud, Matthew Lee, Daniel S Childs, Ayse T. Kendi, Geoffrey Johnson, Matthew K. Tollefson, Stephen A. Boorjian, R. Jeffrey Karnes, Eugene D. Kwon
Journal: Journal of Clinical Oncology (2023)

269 Background: Metastatic visceral involvement in prostate cancer patients conveys a poor prognosis. Survival patterns of site-specific visceral metastasis are poorly understood. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis. Methods: Retrospectively, we identified 200 patients with visceral metastatic prostate cancer. Patients were divided into three groups according to first site detected with visceral metastases; first-site lung metastases, first-site brain metastases, and first-site liver metastases. Visceral metastases were detected on either conventional imaging (CT/MRI), metabolic imaging (C-11 choline), or PSMA PET-CT scan. Follow up duration of our study was 80 months. Results: Clinicopathological variables are shown. The K-M curve of overall survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases compared to patients with first-site brain or liver metastases (p&lt;0.0001). In subset analysis of patients with CRPC, the K-M curve of overall survival, which demonstrates better survival outcomes in patients with first-site lung metastases in comparison with patients with first-site brain or liver metastases (p&lt;0.0001). Conclusions: Our data suggests that prostate cancer patients with visceral metastatic disease have different survival patterns according to the first site detected with visceral metastasis. In our cohort, patients with first-site lung metastasis demonstrated better survival outcomes than patients with first-site brain or liver metastasis. Further studies are warranted. [Table: see text]
The impact of genomic biomarkers on a validated clinical risk prediction model for upgrading/upstaging among men with low-risk prostate cancer.
Authors: Avery Braun, Janet E. Cowan, June M. Chan, John Neuhaus, Peter Carroll, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2023)

262 Background: While active surveillance (AS) is the preferred management strategy for men diagnosed with low-risk prostate cancer (PCa), the inability to distinguish indolent from aggressive tumors in clinically low-risk patients complicates decision-making. Genomic classifiers (GCs) were introduced to improve risk stratification, based on their ability to predict the risk of upgrading or upstaging (UG/US) in this setting. We assessed the impact of GCs on UG/US risk prediction added to a rich clinical model to better guide management decision-making for low-risk patients. Methods: We used multivariate logistic regression and receiver operating characteristic (ROC) curves to develop a prediction model for UG/US in men with low-risk, low-volume intermediate-risk PCa who were potential candidates for AS. The model was developed among 864 men and validated in an independent cohort of 2,267 men with similar risk profiles. After computing areas under the ROC curve (AUC) from these probabilities, we tested the model’s predictive ability with the addition of a series of GCs (OncoType Dx Genomic Prostate Score, Decipher score, and selected Decipher GRID scores) using the logistic model constructed for the development cohort to estimate the predicted probability of UG/US. Results: The prediction model for the development cohort included five diagnostic variables that were significantly associated with risk of UG/US: diagnostic grade (OR 5.83, 95% CI 3.73-9.10), PSA (OR 1.10, 95% CI 1.01-1.20), percent positive cores (OR 1.01, 95% CI 1.01-1.02), TRUS prostate volume (OR 0.98, 95% CI 0.97-0.99), and age (OR 1.05, 95% CI 1.02-1.07). The pooled AUC was 0.72 for 10 iterations of the model. When the addition of GCs was applied to this model, Genomic Prostate Score was independently associated with risk of UG/US (OR 1.42, 95%CI 0.016-0.066, p=0.017). However, the pooled AUC was 0.71, indicating comparable predictive performance to the risk prediction model. Conclusions: The addition of GCs to a validated rich model incorporating detailed clinical variables, when applied to favorable-risk PCa patients, did not substantially improve prediction of UG/US. Our findings suggest that widespread use of biomarkers to guide management or the intensity of follow up may not be supported in men with low-risk, low-volume disease pursuing AS.
Effect of undetectable PSA following SRT for biochemical recurrence on BPFS, FFM, and OS.
Authors: Sophia Scharl, Luca Gartner, Dirk Heinz Gerhard Boehmer, Alessandra Siegmann, Daniel Zips, Reinhard Thamm, Thomas Wiegel
Journal: Journal of Clinical Oncology (2023)

367 Background: Salvage radiotherapy (SRT) alone or in combination with androgen deprivation therapy (ADT) is the only curative treatment option for patients with biochemical recurrence after radical prostatectomy (RP) for prostate cancer. An undetectable post SRT PSA in patients without ADT (&lt;0.1 ng/ml) has been shown retrospectively to correlate significantly with long-term freedom from progression, metastasis free survival and overall survival. The aim of this study was to investigate whether the predictive power of a post SRT-nadir &lt;0.1 ng/ml extends to all subgroups of SRT patients. Methods: Between 1998 and 2018, 698 patients (all pN0/cN0) with persisting PSA or increasing PSA out of the undetectable range (&lt;0.1 ng/ ml) of two German university hospitals received SRT alone without ADT. Exclusion criteria were distant metastases and/or ADT in the interval between RP and/or in combination with SRT. ADT before RP was allowed. All patients received 3D-conformal or intensity-modulated SRT to a median dose of 70.2 Gy. The impact of post-SRT nadir &lt;0.1 ng/ml on biochemical progression free survival (BPFS), freedom from metastases (FFM) and on overall survival (OS) was analyzed by Kaplan-Meier analysis and multivariate Cox regression analysis. 9 subgroups with at least 30 patients per group were analyzed separately (pT2 + R0, pT3 + R0, pT3 + R1, pT2 + Gleason Score ≤ 7, pT3 + Gleason Score ≤ 7, pT3 + Gleason Score ≥ 8, pT3 + Gleason Score ≥ 7 + R1, pT3 + Gleason Score ≥ 7 + pre-SRT-PSA-Wert ≤1,0 ng/ ml and pT2/3 + Gleason Score ≥ 8 + pre-SRT-PSA-Wert ≤1,0 ng/ ml). Results: Median follow-up was 5.6 years. Median PSA before SRT was 0.30 ng/ ml. A post SRT PSA &lt;0.1ng/ml was achieved by 76.6% of patients. In univariate analysis of the entire cohort, post SRT PSA &lt;0.1 ng/ ml was a significant predictor of BPFS (p&lt;0.001), FFM (p&lt;0.001) and OS (p=0.01). Regarding univariate analysis of the subgroups, post SRT PSA &lt;0.1ng/ml was a significant predictor of BPFS in all subgroups (p&lt;0.001), FFM in 6 subgroups (p&lt;0.001 to p=0.03) and for OS in 3 subgroups (p&lt;0.001 to p=0.02). In multivariate analysis of the entire cohort, post-SRT PSA &lt;0.1ng/ml was an independent predictor for BPFS (HR: 7.25, 95%-CI: 5.36-9.81, p&lt;0.001), FFM (HR: 4.21, 95%-CI: 2.00-8.84, p=0.002) and OS (HR: 2.59, 95%-CI: 1.28-5.23, p=0.008). Conclusions: Achieving an undetectable PSA after SRT is an independent predictor of BPFS, FFM and OS. This effect is present in subgroups with favorable (pT2+Gleason score ≤ 7) as well as in those with unfavorable characteristics (pT3+ Gleason score &gt;8). Our findings indicate that ADT could be withheld in a proportion of patients that are candidates for ADT based on their risk factors but achieve an undetectable PSA after SRT. Prospective studies are needed to confirm these results.
High-dose chemotherapy with autologous stem cell transplant (HDCT) for patients (pts) with advanced germ-cell tumors (aGCT): Real-world evidence from a tertiary cancer center in Brazil.
Authors: Gabriel Berlingieri Polho, Mateus Trinconi Cunha, Erick Menezes Xavier, Jamile Almeida Silva, Cassio Murilo Trovo Hidalgo Filho, Nathália de Souza Del Rey Crusoé, Marcelo Junqueira Atanazio, Vivian Horita, Guilherme Fialho de Freitas, David Queiroz Borges Muniz, Vanderson Geraldo Rocha, Jose Mauricio Mota
Journal: Journal of Clinical Oncology (2023)

414 Background: HDCT is a potentially curative treatment for pts with aGCT after conventional-dose chemotherapy (CDC). There is scarce evidence of outcomes from aGCT pts treated with HDCT in low and middle-income countries. Methods: We reviewed our institutional database to identify pts with progressive aGCT referred for HDCT following tumor boards. Medical charts were analyzed to extract clinical data. Log-rank was used to compare survival estimates and Cox proportional hazard to determine effects on overall survival (OS). Exploratory correlation and survival trend analysis used synthetic minority oversampling and Spearman’s rho estimated correlations. Results: From 1/2013 to 8/2022, 35 aGCT pts were referred for HDCT. Median age was 28 years (IQR 25-30). Most pts had testicular primary (84%), non-seminoma histology (87%), 1 prior treatment line (62%), poor-risk by IGCCCG (78%), and intermediate to very high-risk by IPFSG (45%). Of these, 32 pts were deemed eligible after initial evaluation, 25 had mobilization chemotherapy, and 21 received ≥1 cycle of HDCT. Reasons for treatment non-fulfillment included progressive disease and/or performance deterioration due to toxicity. HDCT regimen varied, with most pts receiving TI-CE (62%). Most pts had delays ≥1 month (85%) and ≥2 months (52%) in the scheduled treatment. The 1-year and 2-year OS rates were 42% and 38% in the eligible population, while 70% and 62% among those who had ≥ 1 cycle HDCT. No risk factors correlated with OS in the univariate analysis (Table). Exploratory analysis of oversampled pts treated with ≥1 cycle of HDCT showed correlation of poor IGCCCG (p&lt;0.01) and IPFSG (p=0.03) with OS. Time to mobilization (TTM) was larger in poor-risk IGCCCG pts (0.4 vs. 1.7 months, p&lt;0.01). Four deaths were attributed to HDCT. Conclusions: HDCT was feasible at our tertiary center in Brazil, despite some treatment-related deaths. For pts who had at least 1 HDCT cycle, survival outcomes were similar to the established literature. Significant delays in protocol were noted and correlated with prognostic group risk. [Table: see text]
Tumor transcriptomic profiling of patients (pts) with metastatic castration sensitive prostate cancer (mCSPC) who do versus who do not achieve an optimal PSA response to intensiﬁed androgen deprivation therapy (i-ADT).
Authors: Vinay Mathew Thomas, Nicolas Sayegh, Beverly Chigarira, Georges Gebrael, Yeonjung Jo, Nishita Tripathi, Roberto Nussenzveig, Haoran Li, Kamal Kant Kant Sahu, Clara Tandar, Divyam Goel, Puja Iyer, Benjamin L. Maughan, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2023)

234 Background: Pts with mCSPC receiving i-ADT and achieving a PSA nadir ≤0.2 ng/mL (PSA-L) demonstrate significantly better overall survival (OS) as compared to those with a PSA nadir &gt; 0.2 ng/mL (PSA-H) (Chi AUA 2021, Saad ASCO 2022). We hypothesized that tumor gene expression proﬁle would differ between PSA-L and PSA-H. Methods: In this IRB-approved retrospective study, eligibility criteria included conﬁrmed mCSPC receiving i-ADT with androgen receptor-axis-targeted therapy (ARAT) and availability of RNAseq proﬁling performed by a CLIA-certiﬁed lab of primary prostate biopsies collected before treatment. Pts were divided into 2 groups: PSA-L and PSA-H based on achieving a PSA nadir ≤0.2 ng/mL at any time during treatment course. The DEseq2 pipeline was used to analyze differentially expressed genes between the groups. The data included the Log2 fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p values (q values) for each differentially expressed gene. These results were subjected to Gene Set Enrichment Analysis (GSEA) to identify pathways enriched in each cohort. All bioinformatic analysis was undertaken using R studio v4.2. Results: 78 pts were eligible: 55 were PSA-L, and 23 were PSA-H. The most significantly upregulated pathways in PSA-L were the TNFA signaling, androgen response (AR), estrogen response, and interferon-alpha response pathways. The most upregulated pathways in PSA-H were epithelial-mesenchymal transition, coagulation, and bile acid metabolism pathways. Normalized enrichment scores are reported in the table. Differential individual gene expression profiles will be presented at the meeting. Conclusions: These hypothesis-generating data show that mCSPC pts on i-ADT with PSA-L have distinct baseline tumor gene expression profiles, such as upregulation of AR signaling, compared to pts with PSA-H. After external validation, these findings may help personalize medicine prior to initiation of therapy in pts not expected to achieve PSA-L. [Table: see text]
Genomic alterations in metastatic renal cell carcinoma (mRCC): Impact on survival and clinical outcomes.
Authors: Jennifer King, Rebecca Hassoun, Sandra K. Althouse, Christopher A. Fausel, Bryan P. Schneider, Theodore F. Logan, Nabil Adra
Journal: Journal of Clinical Oncology (2023)

700 Background: Genomic alterations in RCC can serve as biomarkers for response to therapy. Wild type VHL has shown inferior response to VEGF inhibitors, while patients (pts) with mutated VHL have improved outcomes with immunotherapy (IO)/tyrosine kinase inhibitor (TKI) therapy. We describe the impact of genomic alterations on outcomes and response to front-line therapy. Methods: Pts with mRCC who underwent genomic sequencing between 2015-2022 at Indiana University and were treated with front-line therapy were included. Kaplan-Meier method was used to analyze progression free survival (mPFS) and overall survival (OS) using the log rank test to compare groups. Results: 141 pts were included. Median age was 58yrs (range, 24-81). Tumor histology was 68% clear cell, 10% papillary, 9% unclassified, 1% chromophobe, 1% poorly differentiated, and 9% other. 18% of pts had sarcomatoid features; 13% had rhabdoid. 47% pts had metastasis at diagnosis and 53% at relapse. Metastasis sites were lungs 60%, regional lymph nodes (LNs) 41%, bone 36%, distant LNs 21%, liver 17%, and brain 8%. IMDC risk was 18% good, 48% intermediate, 17% poor, and 17% unknown. Front-line therapy was IO/IO in 21%, IO/TKI in 18%, single-agent TKI in 29%, single-agent IO in 6%, and other in 26%. Genetic alterations included VHL in 50%, PBRM1 in 29%, SETD2 in 23%, BAP1 in 16%, and TP53 in 15%. Median follow-up was 2.74yrs (range 0.1-18.6). Overall mPFS with first line therapy was 1.2yrs (95%CI 0.9-1.5). 2-yr OS was 80% (95%CI: 71-86). For pts with a VHL mutation, mPFS was 1.4yrs (95% CI; 0.9-1.8) compared to 0.9yrs (0.5-1.4) for pts without (p=0.38). 2-yr OS for pts with a VHL mutation was 93% (95% CI: 82-97) vs. 68% (95%CI: 54-78) for pts without (p=0.01). No other mutations impacted overall mPFS or 2-yr OS. mPFS for pts treated with IO/IO was 0.6yrs (95%CI 0.3-0.9) vs. 0.9yrs (95%CI 0.5-1.4) for IO/TKI (p=0.09). 2-yr OS for pts treated with IO/IO was 70% (95% CI 44-85) compared to 94% (95% CI 65-99) for IO/TKI (p=0.29). For pts with SETD2 mutations treated with IO/IO, mPFS was 0.7yrs (95%CI 0.3-1.2) vs. 1.4yrs (95%CI 0.8-1.9) for IO/TKI (p=0.01). For pts with BAP1 mutations treated with IO/IO, mPFS was 0.4yrs (95%CI 0.2-1.2) vs. NE (95%CI 0.2-NE) for IO/TKI (p=0.04). The table outlines outcomes by genomic mutation and therapy. Conclusions: VHL mutation was associated with improved 2-yr OS. Pts with SETD2 and BAP1 mutations treated with IO/TKI had improved mPFS, though no differences in OS. [Table: see text]
Identifying prostate cancer patient subgroups based on their preferences for key attributes of androgen deprivation therapies.
Authors: Sean P. Collins, Martine C. Maculaitis, Brett Hauber, Elke Hunsche, Lewis Kopenhafer, Esmond Nwokeji, Kathleen M. Beusterien
Journal: Journal of Clinical Oncology (2023)

94 Background: Androgen deprivation therapies (ADTs) for prostate cancer (PC) vary in delivery mode, T (testosterone) surge occurrence, time to T recovery, adverse event profile, and costs. Data are limited on how men differ in their evaluation of ADT attributes. This study identified subgroups of men who vary in their preferences for key ADT attributes. Methods: A cross-sectional survey of US men aged &gt;40 years, who had healthcare coverage for the past 3 years and self-reported a PC diagnosis, were recruited via healthcare research panels. Men were ineligible if they did not know/recall whether they had received ADT or were unable to complete the survey independently. Quotas ensured an approximate even split of ADT-experienced and ADT-naïve men. A discrete choice experiment assessed preferences for ADT attributes. In a series of choice tasks, men were presented with 2 ADT treatment profiles side-by-side and asked to select the one they prefer. Hierarchical Bayes models computed attribute level preference weights. Relative importance (RI), based on differences between the most and least favorable attribute level preference weight and standardized to sum to 100%, was estimated for each attribute; the higher the RI value, the more influential an attribute is to treatment choice. Latent class analysis (LCA) identified groups (Gs) of men with similar ADT preferences. Results: 304 men were included in the analyses, their mean age was 64.4±7.2 years, and 16.8% were African American. Mean PC duration was 5.4±4.8 years, 55.3% reported organ-confined PC, and 49.0% had prior ADT use. LCA identified 4 preference Gs. While impact on sexual activity was most important to G1, out-of-pocket (OOP) costs, mode of administration, and time to T recovery were choice drivers for G2. Mode of administration and OOP costs predominated in importance for G3 and G4, respectively. More than half of men in G1 and G3 were &lt;65 years; G1, but not G3, included mainly men who planned to be sexually active. G2 and G4 were predominantly composed of men aged ≥65 years who often had Medicare insurance. Conclusions: Younger, sexually active men consider the potential impact on sexual activity when choosing PC therapy, while for older men administration burden or OOP costs are important choice drivers. Thus, ADT attributes often vary in salience to men and should be considered in shared PC treatment decision-making. [Table: see text]
Phase 2 study (AARDVARC) of AZD4635 in combination with durvalumab and cabazitaxel in patients (pts) with progressive metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Teresa Alonso Gordoa, Michael Moses Goodman, Christof Vulsteke, Guilhem Roubaud, Jingsong Zhang, Mamta Parikh, Josep M. Piulats, Analía Azaro, Gareth D James, Riccardo Cavazzina, Eric Gangl, Jeff Thompson, Gayle Pageau Pouliot, Rakesh Kumar, Christopher Sweeney
Journal: Journal of Clinical Oncology (2023)

173 Background: Pts with mCRPC who progress on docetaxel and new hormonal agents (NHAs) have few therapeutic options. In the CARD study of cabazitaxel, 35.7% of pts had PSA responses and 36.5% of pts had tumor responses. While immune checkpoint inhibitors have limited single-agent activity in mCRPC, the combination of the adenosine 2A receptor antagonist, AZD4635, with durvalumab may improve response to chemotherapy. This study assessed AZD4635 in combination with durvalumab (Arm A) or with durvalumab + cabazitaxel (Arm B) in pts with mCRPC. We report interim analysis results from Arm B (Arm A to be reported elsewhere). Methods: Eligible pts had histologically confirmed mCRPC, disease progression ≤6 months prior to enrollment, and were previously treated with docetaxel and 1 NHA. Pts received AZD4635 75 mg PO QD + durvalumab 1500 mg IV Q3W + cabazitaxel Q3W (dosed per locally approved label) for up to 10 cycles. The primary endpoint was radiographic progression-free survival (rPFS), by RECIST v1.1 (soft tissue) or PCWG3 (bone). Secondary endpoints included safety, pharmacokinetics, confirmed PSA 50 response, and objective response rate by RECIST v1.1. A futility analysis was planned based on PSA 50 responses (confirmed + unconfirmed) after approximately 30 pts were treated. Results: As of August 10, 2021, 28 pts received AZD4635 + durvalumab + cabazitaxel, and 21 pts were still on treatment. Most common adverse events (AEs) possibly related to treatment were nausea (50.0%), diarrhea (46.4%), asthenia, and vomiting (each 28.6%). Treatment-related febrile neutropenia occurred in 7.1% pts. Twelve (42.9%) pts had a serious AE possibly related to treatment. One AE possibly related to treatment led to death (myositis). Exposures of cabazitaxel and/or durvalumab did not change when combined with AZD4635. Median rPFS was 4.4 months (95% CI: 4.2–not calculable) with low percent maturity. Of 28 PSA-evaluable pts, 8 (28.6%) had PSA 50 responses (4 confirmed). There were 5 unconfirmed partial responses by RECIST v1.1. Conclusions: Although efficacy data are immature, enrollment was stopped for futility. Safety of the combination was consistent with the known safety profiles of the individual agents. Clinical trial information: NCT04089553 .
Adjuvant immunotherapy in renal cell carcinoma: A systematic review and meta-analysis of randomized clinical trials.
Authors: Emily Huang, Carlos Riveros, Sanjana Ranganathan, Zachary Klaassen, Brian I. Rini, Christopher J.D. Wallis, Raj Satkunasivam
Journal: Journal of Clinical Oncology (2023)

671 Background: There has been interest in adjuvant immune checkpoint inhibition (ICI) following surgical resection in patients with high-risk renal cell carcinoma (RCC) given high recurrence rates and approvals of ICI in metastatic RCC. The primary objective of this analysis was to synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant ICIs for patients with RCC. Methods: This systematic review was performed according to the PRISMA guidelines. The protocol was registered in PROSPERO (CRD42022361599). We searched PubMed, EMBASE, and relevant conference proceedings to identify phase III randomized controlled trials (RCTs) comparing adjuvant ICI versus placebo/observation. The primary outcome of interest was DFS. Results: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I2=64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (HR 0.85, 95% CI 0.69-1.04), there was significant benefit among patients with positive PD-L1 expression (HR 0.72, 95% CI 0.55-0.94) or sarcomatoid features (HR 0.59, 95% CI 0.38-0.91). Conclusions: The evidence base to date regarding ICI as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PDL1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.